Team:NRP-UEA-Norwich/ModelingAndSoftware
Modelling and Software
While we were bringing all the parts together in the lab, a lot of unanswered questions were raised: What do glycogen and starch molecules really look like? How will over-expressing GlgX and GlgB (de-branching and branching enzymes) affect the global structure of glycogen? How will this branching and debranching process take place? And, how will the acyltransferases add the acyl groups into the glycogen/starch molecule and in which position? Will this addition affect the way the glycogen molecule grows?
Thanks to computers, software and maths, we were able to predict the outcomes of these processes to help us understand what might happen in the lab.
Software: Glyco2D
We used glycogen as a model system to gain a better understanding of the parameters involved in carbohydrate structure, branching and modification.
We built Glyco2D based on the mathematical model that described the structural properties of glycogen based on different parameters such as chain length, branching degree and the number of tiers1.
Then we used the software to model the putative changes in glycogen structure depending on the location of the modification. Our aim was to produce carbohydrate molecules with 5-10% of the residues modified since this level of butrylation (achieved by chemical modification) has positive benefits to the colons of rats 2.
You can learn more by clicking on the image to the right.
3D models
We build 3D models of carbohydrates to get a better understanding of the effect of branching degree and chain length on the real structure. We used the
We developed a pipeline to 3D print these molecules. After several attempts, we managed to have our own 3D printed glycogen!
You can learn more by clicking on the image on the right.
Kinetic modelling
To analyse the efficiency of the branching (GlgB) and debranching (GlgX) enzymes in glycogen production, we generated a set of differential equations to explain glycogen biosynthesis. We also incorporated all the enzymes involved in the pathway starting from taking the glucose from the medium 3.
This model helped us to understand the outcome of overexpressing GlgB and GlgX in the lab in an E. coli cell.
You can learn more by clicking on the image on the right.
References
1. Meléndez-Hevia E., Waddell T.G., and Shelton E.D., 1993, Optimization of molecular design in the evolution of metabolism: The glycogen molecule , Biochem Journal, 295, p. 477–83
2. Bajka B.H., Clarke J.M., Topping D.L., Cobiac L., Abeywardena M.Y., and Patten G., 2010, Butyrylated starch increases large bowel butyrate levels and lowers colonic smooth muscle contractility in rats , Nutrition Research, 30, p. 427–34
3. Wilson WA, Roach PJ, Montero M, Baroja-Fernández E, Muñoz FJ, Eydallin G, Viale AM, Pozueta-Romero J (2010) Regulation of glycogen metabolism in yeast and bacteria. FEMS Microbiology Reviews 34:952–85
